De novo HNF-1 beta gene mutation in familial hypoplastic glomerulocystic kidney disease

Pediatr Nephrol. 2002 Dec;17(12):1021-6. doi: 10.1007/s00467-002-0975-2. Epub 2002 Nov 14.


Mutations in the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1 beta are associated with maturity-onset diabetes of the young (type V), non-diabetic renal disease, and occasionally genital malformations in females. Recently, familial hypoplastic glomerulocystic kidney disease (GCKD) has been added to the clinical spectrum of HNF-1 beta gene mutations. Familial hypoplastic GCKD is a rare, dominantly inherited disorder characterized by small kidneys containing glomerular cysts, abnormal pelvicalyceal anatomy, and chronic renal failure. A family with hypoplastic GCKD occurring in the father and the daughter was screened for mutations in the HNF-1 beta gene. The sequence of exon 4 of the HNF-1 beta gene revealed a C insertion at codon 334 resulting in a frameshift mutation (P334fsinsC) in two family members. The P334fsinsC allele co-segregated with hypoplastic GCKD in the family. Oral glucose tolerance testing was normal in the 11-year-old girl. In her 38-year-old father, impaired glucose tolerance was detected. These studies provide further evidence that familial hypoplastic GCKD is associated with HNF-1 beta gene mutations. HNF-1 beta gene mutation screening may prove useful in patients with small cystic kidneys and chronic renal failure, in whom a definite renal diagnosis could otherwise only be established by renal biopsy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Austria
  • DNA / biosynthesis
  • DNA / genetics
  • DNA-Binding Proteins*
  • Female
  • Frameshift Mutation / genetics*
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Humans
  • Infant
  • Kidney Diseases / diagnostic imaging
  • Kidney Diseases / genetics*
  • Kidney Diseases / pathology
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / genetics
  • Kidney Glomerulus / diagnostic imaging
  • Kidney Glomerulus / pathology
  • Male
  • Nuclear Proteins*
  • Pedigree
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Ultrasonography


  • DNA-Binding Proteins
  • HNF1A protein, human
  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Nuclear Proteins
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta
  • DNA